Clinical and biological effects of gamma interferon and the combination of gamma interferon and interleukin-2 after autologous bone marrow transplantation.
Interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) have shown synergistic immunomodulatory and anti-tumor effects in preclinical studies. The present study was designed to assess the effects of the combination of these cytokines after autologous bone marrow transplantation (ABMT). Ten patients received rIFN-gamma alone and 13 patients the combination of rIFN-gamma + rIL-2. Patients received transplants because of lymphoma (10 patients), acute leukemia (3 patients) or solid tumors (10 patients). Immunotherapy was started at a median of 67 days after ABMT. All patients received either 5 x 10(6) (8 pts) or 10 x 10(6) IU/m2 (16 pts) rIFN-gamma by subcutaneous injection 3 times weekly for 14 weeks. rIL-2 therapy consisted of 5 cycles of continuous intravenous infusion of 12 x 10(6) IU/m2/day starting 1 week after administration of rIFN-gamma. In the rIFN-gamma group, toxicity was mild and some biological changes were seen (NK/LAK activation, increase of phagocytosis and of NBT reduction). The combination of rIFN-gamma with rIL-2 did not increase the usual rIL-2 toxicity. NK/LAK cytotoxicity was strongly activated after the first cycle of rIL-2 and was maintained until the end of therapy. Granulocyte chemotaxis was defective after cycle 1 but recovered thereafter. We conclude that the administration of rIFN-gamma + rIL-2 is feasible after ABMT. Our data suggest that the combination may have prolonged the immunologic activation provided by rIL-2 and some improvement of the deleterious effects of rIL-2 on granulocyte functions was achieved. Controlled studies are warranted to assess the impact of this strategy on biological response and patient outcome.
Vey
N
N
Institut Paoli-Calmettes and INSERM Unit 119, Marseille, France.
Viens
P
P
Fossat
C
C
Olive
D
D
Sainty
D
D
Baume
D
D
Stoppa
A M
AM
Bouabdallah
R
R
Brandely
M
M
Gastaut
J A
JA
Maraninchi
D
D
Blaise
D
D
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D010865:Pilot Projects; D011994:Recombinant Proteins; D012307:Risk Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma